The Midwest Regional Center for Excellence in Biodefense and Emerging Infectious Diseases Research (MRCE) is a consortium of leading Midwest institutions that will serve the biodefense research and training needs for Region VII as well as parts of Ohio. The founding members of the MRCE are Washington University in St. Louis (site of the administrative core), Case Westem Reserve University, St. Louis University, the Midwest Research Institute, and the University of Missouri. The major objective of the MRCE is to harness outstanding scientists from the best institutions to focus on cdtical clinical issues in biodefense and emerging infectious diseases. Our goal is research that will have an immediate impact on the nation's public health, and will provide the scientific base for a strong biodefense effort. The Strategic Plan for the MRCE centers on a comprehensive multi-institutional effort on the biology of poxviruses. The conjunction of extraordinarily strong existing programs in clinical research on smallpox vaccination and basic research on poxviruses and innate immunity to viral infections, will allow us to answer the critical questions about the biology of vaccinia infection, and the risks of smallpox vaccination. Our second program focuses on plague, and will use state of the art platforms in genetics and structural biology to study the pathogenesis of Yersinia pestis, and design a new class of antibacterial agents, the pilicides, for the treatment of plague. The backbone of the MRCE effort are Core Facilities designed to serve the biodefense needs of Region VII and the nation. Foremost among the Cores is the Washington University Genome Sequencing Center, the largest sequencing center in the United States. The MRCE Strategic Plan will consolidate the high throughput sequencing and genotyping services for all the Regional Centers for Excellence at the MRCE, resulting in significant cost savings. Finally, the MRCE will lead the effort to recruit new investigators to clinical and basic research in biodefense and train them in how to conduct this research safely and securely through three distinct Career Development Programs, including a one-of-a-kind fellowship program that will train postdoctoral fellows in the life sciences to become biosafety officers. The MRCE is uniquely positioned to serve Region VII and the nation through an exceptional program that addresses the most immediate and urgent national biodefense needs.